Formaldehyde and Formaldehyde Releasing Preservatives Revisited Sharon E

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Formaldehyde and Formaldehyde Releasing Preservatives Revisited Sharon E ALLERGEN FOCUS FORMALDEHYDE AND FORMALDEHYDE RELEASING PRESERVATIVES REVISITED SHARON E. JACOB, MD, ELIZABETH A. MALDONADO, AND ELISE M. HERRO, MD with the immune system (sensitization to a chemical and then elicitation of a dermatitis with re-exposure); and that it can occur at any point in time, even to something that the patient has been using regularly for a short period of time or even intermittently for years. In certain cases, the topics of the other key players, such as irritant contact der- matitis (ICD) and contact urticaria, may be explained, as history (not patch testing) can point to these as the cor- rect diagnoses for the patient. It is im- portant to note that ICD, the most prevalent form of contact dermatitis, can at times precede or be a concomi- tant diagnosis with ACD.4,5 Unlike ACD, ICD is not immune-mediated. It occurs secondary to contact with an ir- ritating or abrasive substance. Contact urticaria (CU)(wheal and flare reac- tion), on the other hand, represents the least prevalent form of contact der- matitis. It is important to note that CU is an immune-mediated phenomenon, whose hallmark is an IgE and mast cell- llergic Contact Dermatitis (ACD) is an important disease, mediated immediate-type hypersensi- which notably affects 14.5 million Americans each year.1 The tivity reaction. We acknowledge this Aeconomic impact of this disease is high in terms of both pa- form of hypersensitivity due to the tient morbidity and loss of income, school and work, not to mention severity of the potential deleterious significant expenditures for visits to health care providers and for anaphylactic-type reactions and direct Sharon E. Jacob, MD medicaments.1 Once patch testing is performed and a culprit has the reader to key sources.6,7,8 been identified, education becomes the critical intervention to ensure In this column, we highlight ACD adherence to an avoidance regimen. With allergen avoidance, remis- and explore top relevant allergens, re- sion of the dermatitis ensues. Patients who are unable to comply with gional-based dermatitis presentations, the avoidance regimen become at risk for recurrent or sustained der- topic-based dermatitis presentations matitis or progression to a systematized presentation.2,3 In fact, edu- and clinical tips and pearls for diagnosis Elizabeth A. Maldonado cation of the patient often begins before the diagnostic patch test is and treatment. ever placed, to ensure patients have an appropriate understanding of potential outcomes and their central role in both their disease and FORMALDEHYDE AND FORMALDEHYDE- treatment. RELEASING PRESERVATIVES At the initial consultation, patients are often taught about the The mention of formaldehyde elic- Elise M. Herro, MD pathophysiology of ACD — its delayed presentation; its relationship its visions of biopsy specimen bottles 24 JUNE 2011 | SKIN & AGING | www.skinandaging.com ALLERGEN FOCUS and medical students training on ca- medicament and personal hygiene Table 1. SOURCES OF FORMALDEHYDE OR FRPs9,14,31 davers in anatomy lab; however, there manufacturing today (Table 1). are many more potential daily en- Personal hygiene products (FRPs) counters with this chemical that often FORMALDEHYDE ALLERGY Shampoo go unrecognized. Formaldehyde is an As with all contact allergens, the effective and inexpensive biocidal pre- more ubiquitious the usage, the more Conditioner servative that has long been used in likely it is for it then to be a top sensi- Body wash the preparation of medicaments and tizer, and formaldehyde is no excep- Hand soap cosmetic products. Early on, it was a tion. In 1939, Paul Bonnevie published frontrunner in providing cosmetics the first standard series of patch test Lotion/cream manufacturers options to comply with antigens,14 and of his 21 original aller- Baby wipes increasing safety regulations from the gens, six (including formaldehyde) are Cosmetics Food, Drug, and Cosmetic Act of still used in today’s patch-testing kits. 1938.9 Personal hygiene product con- In fact, unfortunately, formaldehyde is Mascara tamination had been identified as a se- a top contact allergen today for both Blush rious public health concern and adults and children, with increasing Foundation measures had to be taken to ensure the rates of sensitization.9,15,16,17 A recent safety of the consumer. For example, publication by the North American Disinfectants/Household cleaners Morse et al described six cases of sep- Contact Dermatitis Group (NACDG) Fabric softeners ticemia reported in a medical intensive reported that 9% of more than 4,400 Medicaments care unit, resulting from Klebsiella patients patch tested between 2005 and pneumoniae contamination of the 2006 were formaldehyde allergic.18 In Permethrin cream nurses’ lanolin hand cream, whose for- addition, 10.3% of the total tested pos- Topical steroids (FRPs) mulation failed to include appropriate itive to the formaldehyde-releasing Anhidrotics (FRPs) biocidal additives/preservatives.10 preservative (FRP), quaternium-15, Formaldehyde offered and contin- which was significantly higher than the Wart remedies (FRPs) ues to offer an attractive germicidal prior 2-year cycle, as well as the prior Vaccines solution for cosmetic, medicament and 10 years (1994 to 2004).18 Moreover, Inactivated Polio Vaccine32 therapeutic formulations. It also has both formaldehyde and quaternium- antiviral properties; for example, the 15 reactions were reported as being at Anthrax Vaccine Adsorbed33 Centers for Disease Control and Pre- least 93% clinically relevant, which is a Diphtheria and Tetanus Toxoids and Acellular Pertussis vention (CDC) found that an 8% con- pivotal point in patch test interpreta- Vaccine Adsorbed34 centration of formalin (a water-based tion. Clinical relevance determines to *Hepatitis A Vaccine35 solution of formaldehyde) was enough what extent a positive allergen could to inactivate poliovirus within 10 be responsible for the patient’s clinical Food/Drink Maple syrup Formaldehyde offered and continues to offer an attractive Smoked ham germicidal solution for cosmetic, medicament and Instant crystal coffee therapeutic formulations. Aspartame (through metabolism) Clothing minutes.11 Of interest, it was this find- presentation. In order to assign rele- Permanent press finish ing that led to the development of the vance, the patch test provider and pa- Wrinkle resistant successful inactivated polio vaccine tient must work together to find the Corduroy (Salk vaccine) in 1952.12 Also along source of exposure and confirm its rel- those same lines, formaldehyde was evance by proving clearance of the Miscellaneous historically important in limiting the dermatitis through source avoidance. Tanned leather spread of the bubonic plague in San Since sources of formaldehyde and Plywood/particle board Francisco, when an outbreak occurred FRPs abound, from household at the turn of the 20th century.13 A cleansers to personal hygiene products Glues and adhesives concoction of lime and formaldehyde and medicaments, this can prove to be Smog was spread over Chinatown to quaran- a difficult task. Cigarette smoke tine it and reduce its spread.13 Even In order to regulate this allergen, the now, as the number of available preser- European Union had issued a Cosmet- Embalming fluid vatives has increased five fold in the ics Directive, which stated that the Tissue specimen preservation last century, formaldehyde maintains a warning label, ‘contains formaldehyde,’ *Formalin: not more than 0.1 mg/mL significant and important role in must be placed on all products contain- JUNE 2011 | SKIN & AGING | www.skinandaging.com 25 ALLERGEN FOCUS tained.9,24 Nevertheless, with time, many lergEAZE (AllergEAZE Inc., Port Table 2. FORMALDEHYDE-RELEASING FRPs were reported as contact allergens Washington, NY), while sodium hy- PRESERVATIVES (FRPS) as well, whether due to release of droxymethyl glycinate is not commer- Bromonitropropane diol (Bronopol) formaldehyde or the chemical structure cially available. Diazolidinyl urea (Germall II) itself.19,25 As mentioned above, the most DMDM hydantoin (Glydant) sensitizing of the FRPs, quaternium-15, PEARLS Imidazolidinyl urea (Germall) is used both commercially and industri- Dermatitis Distribution ally and is consistently ranked as a top Because formaldehyde or formalde- Quaternium-15 (Dowicil 75) contact allergen.9,25,26 In contrast, a newly hyde-releasing substances are included Tris (hydroxymethyl) nitromethane (Tris Nitro) recognized FRP is sodium hydrox- in such a wide array of products, clini- Sodium hydroxymethylglycinate (SHMG) ymethylglycinate (SHMG), and while cal distribution of a patient’s dermatitis not widely researched, it is used in many becomes critical in determining rele- ing formaldehyde or chemicals that re- child care products marketed as “nat- vant sources of exposure. For instance, lease formaldehyde if the free formalde- ural” or “organic,” as well as medica- formaldehyde exposure from textiles, hyde concentration exceeds 0.05% by ments and cosmetics.15,21 Contact allergy ie, permanent press or wrinkle-resistant weight (500 ppm).19 In addition, the to formaldehyde was recently reported clothing, can result in a dermatitis in European concentrations of FRPs are in three toddlers, with SHMG being the regions where clothing is likely to rub, limited by a maximum allowed concen- only relevant exposure to FRPs, as test- such as body folds.9 In addition, sys- tration.20 Currently, the FDA does not ing for additional releasers yielded neg- temic exposure by ingestion of con-
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